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Keywords = follicular regeneration

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17 pages, 268 KB  
Article
Assessment of the Impact of Cold Atmospheric Plasma Application on Wound Healing in Streptozotocin-Induced Diabetic Rats
by Emine Ersozlu, Emine Iyigun and Muhammed Kamil Turan
Antioxidants 2026, 15(6), 760; https://doi.org/10.3390/antiox15060760 - 16 Jun 2026
Viewed by 345
Abstract
Diabetic wounds remain a major clinical challenge due to impaired healing associated with persistent inflammation, oxidative stress, and microvascular dysfunction. Plasma-based therapies have emerged as promising approaches for promoting tissue repair; however, comparative evidence regarding different plasma modalities remains limited. In this study, [...] Read more.
Diabetic wounds remain a major clinical challenge due to impaired healing associated with persistent inflammation, oxidative stress, and microvascular dysfunction. Plasma-based therapies have emerged as promising approaches for promoting tissue repair; however, comparative evidence regarding different plasma modalities remains limited. In this study, we evaluated and compared the effects of atmospheric pressure cold plasma (APCP) and plasma-activated water (PAW) on wound healing in a streptozotocin-induced diabetic rat model. Forty Wistar albino rats were randomly assigned to five groups: isotonic wet dressing, hydrocolloid dressing, APCP treatment, PAW application, and a non-diabetic control group. Wound healing was assessed using macroscopic evaluation, histopathological analysis, and biochemical measurements of systemic oxidative status. PAW treatment significantly accelerated wound closure during the early healing phase compared with conventional dressing methods (p < 0.05). Histological findings demonstrated enhanced re-epithelialization, increased collagen deposition, and improved follicular regeneration in the PAW group. Although total oxidant status (TOS) did not differ significantly among groups (p = 0.996), total antioxidant status (TAS) was significantly increased following PAW treatment (p < 0.05), indicating a more favorable systemic antioxidant profile. These findings suggest an association between improved wound healing and a more favorable systemic antioxidant profile following PAW treatment. However, because local wound-level redox parameters and molecular markers were not assessed, the contribution of redox-related mechanisms remains to be clarified. Moreover, PAW demonstrated superior therapeutic efficacy compared with direct plasma application, highlighting its potential as a non-invasive approach for diabetic wound management. Full article
32 pages, 4915 KB  
Article
Human Stem Cell-Derived Conditioned Media as a Regenerative Cosmetic Ingredient: A Preclinical Characterization and Exploratory Topical Evaluation
by David Cajthaml, Alison Ingraldi and Aaron J. Tabor
Cosmetics 2026, 13(2), 91; https://doi.org/10.3390/cosmetics13020091 - 11 Apr 2026
Viewed by 1919
Abstract
Background/Objectives: Amniotic-derived biologics have emerged as powerful modulators of tissue regeneration. This study evaluates the composition and characteristics of a human stem cell-conditioned media (hSCCM) that is a sterile, cell-free, amniotic-derived solution, and the presumed efficacy of hSCCM as an active ingredient in [...] Read more.
Background/Objectives: Amniotic-derived biologics have emerged as powerful modulators of tissue regeneration. This study evaluates the composition and characteristics of a human stem cell-conditioned media (hSCCM) that is a sterile, cell-free, amniotic-derived solution, and the presumed efficacy of hSCCM as an active ingredient in an enriched cosmetic lotion. Methods: Data from preclinical benchtop studies and an exploratory observational assessment were reviewed. First, an investigation of the active ingredient, hSCCM, was completed. Flow cytometry assays were completed for mesenchymal stem cell (MSC) characterization. Cellular proliferation assays were conducted to evaluate concentration response, shelf life, and temperature stability. ELISA and LC-MS/MS were used to specify and detail the proteomics of the hSCCM. Second, the hSCCM-enriched lotion’s cosmetic safety and efficacy were evaluated. Preliminary microbial, stability, and early-stage nonclinical retrospective user evaluation of the hSCCM-enriched lotion was conducted to help characterize the cosmetic and evaluate topical safety and efficacy. Results: Flow cytometry demonstrated alignment with ISCT (International Society for Cell and Gene Therapy) characterization for MSCs. Initial in vitro data demonstrated enhanced proliferative effects at hSCCM concentrations as low as 5% (p-value < 0.0001); no statistically significant trend in proliferative capability in aged samples (p-value = 0.79), and no significant effect on proliferative capability when exposed to acute temperature changes (p-values all above 0.05) were observed. Proteomic characterization showed an enriched amniotic-derived solution. Microbial testing of the enriched lotion demonstrated success with multiple unique preservative formulations. hSCCM-enriched lotion demonstrated stability across acute cold- and heat-stress representative scenarios. An exploratory retrospective observational analysis revealed promising trends. Conclusions: The hSCCM demonstrates topical efficacy across in vitro dermal and follicular assays via proliferative and regenerative mechanisms and protein enrichment. The enriched lotion showed success in early-stage microbial and stability testing and demonstrates positive trends in topical skin outcomes. These findings support their potential translational application in dermatologic and aesthetic usage, and broader integumentary contexts. Full article
(This article belongs to the Section Cosmetic Formulations)
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20 pages, 2680 KB  
Review
Bio-Nanovesicle-Based Approaches for Hair and Skin Regeneration: An Updated Concise Review
by Ramya Lakshmi Rajendran, Danyal Reyaz, Atharva Anand Mahajan, Chae Moon Hong, Kandasamy Nagarajan ArulJothi, Byeong-Cheol Ahn and Prakash Gangadaran
Cells 2026, 15(7), 617; https://doi.org/10.3390/cells15070617 - 30 Mar 2026
Viewed by 1111
Abstract
Skin and hair follicles regenerate through coordinated stem cell niches and cyclic signaling associated with transitions among anagen, catagen, and telogen phases. In alopecia and chronic skin diseases, follicular miniaturization, immune dysregulation, persistent inflammation, impaired vascularization, and a compromised stratum corneum barrier limit [...] Read more.
Skin and hair follicles regenerate through coordinated stem cell niches and cyclic signaling associated with transitions among anagen, catagen, and telogen phases. In alopecia and chronic skin diseases, follicular miniaturization, immune dysregulation, persistent inflammation, impaired vascularization, and a compromised stratum corneum barrier limit the effectiveness of conventional topical and systemic therapies. Bio-nanovesicles (BNVs), including natural extracellular vesicles such as exosomes and microvesicles, as well as engineered artificial or hybrid nanovesicles, offer a targeted, cell-free delivery platform for miRNAs, proteins, and growth factors. By modulating key pathways—Wnt/β-catenin, PI3K/AKT, MAPK/ERK, and TGF-β/BMP—BNVs have the potential to restore regenerative crosstalk, enhance angiogenesis, and help initiate hair and skin repair. Full article
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18 pages, 685 KB  
Review
Fibroblast Growth Factor-7 and Hair Biology: Bridging Basic Science and Therapeutic Applications
by Huey-Chun Huang, Wang-Ju Hsieh, Ivona Percec and Tsong-Min Chang
Curr. Issues Mol. Biol. 2026, 48(1), 102; https://doi.org/10.3390/cimb48010102 - 19 Jan 2026
Cited by 2 | Viewed by 2322
Abstract
Alopecia profoundly impacts psychological well-being and quality of life, yet current therapeutic options such as minoxidil and finasteride exhibit limited efficacy. Fibroblast growth factor 7 (FGF-7), also known as keratinocyte growth factor (KGF), is a paracrine growth factor secreted by dermal papilla cells [...] Read more.
Alopecia profoundly impacts psychological well-being and quality of life, yet current therapeutic options such as minoxidil and finasteride exhibit limited efficacy. Fibroblast growth factor 7 (FGF-7), also known as keratinocyte growth factor (KGF), is a paracrine growth factor secreted by dermal papilla cells that specifically activates the epithelial receptor FGFR2b. Receptor engagement triggers multiple downstream signaling cascades, including the MAPK/ERK, PI3K/Akt, and Wnt/β-catenin pathways, promoting keratinocyte proliferation, stem cell activation, and the transition of hair follicles into the anagen phase. Both in vitro and in vivo animal studies consistently demonstrate that FGF-7 accelerates telogen-to-anagen transition and enhances follicular regeneration. FGF-7 acts synergistically with insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) to sustain nutrient delivery and cell proliferation. Human scalp studies further reveal a strong association between the FGF-7/FGFR2b signaling and follicular activity; however, clinical trials remain scarce. Topical application of FGF-7 has demonstrated an excellent safety profile, whereas systemic administration necessitates careful monitoring. Future directions include the development of engineering to extend the systemic half-life, advanced delivery systems, and gene or mRNA-based therapeutic approaches. Thus, the FGF-7/FGFR2b axis is a highly compelling molecular target for next-generation hair regeneration therapies. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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10 pages, 1044 KB  
Article
Molecular Regulation of Secondary Hair Follicle Stem Cell by S100a4 in Cashmere Goat
by Xinyue Liang, Bohan Liu, Jiayi Wang, Yanlei Liu, Yiping Wei, Hongji Yu, Junpeng Zhang, Shuyi Zhang and Huiling Xue
Int. J. Mol. Sci. 2026, 27(2), 849; https://doi.org/10.3390/ijms27020849 - 15 Jan 2026
Viewed by 759
Abstract
Secondary hair follicle stem cells (HFSCs) are essential for cashmere fiber regeneration, yet the molecular mechanisms governing their activation and lineage progression remain poorly understood. Here, we identify S100a4 as a key regulator of secondary HFSCs in cashmere goat. S100a4 expression peaks during [...] Read more.
Secondary hair follicle stem cells (HFSCs) are essential for cashmere fiber regeneration, yet the molecular mechanisms governing their activation and lineage progression remain poorly understood. Here, we identify S100a4 as a key regulator of secondary HFSCs in cashmere goat. S100a4 expression peaks during anagen and is markedly enriched in secondary HFSCs relative to hair matrix cells (HMCs), suggesting a role in initiating follicle regeneration. Functional assays show that S100a4 promotes HFSCs into a dynamically regulated state that activates stem cell competence while facilitating differentiation, with overexpression upregulating epidermal and follicular differentiation markers (Ivl, Cux1, K14, Klk5), as well as pluripotency genes (Itga6, Krt15), while knockdown suppresses these programs. Proteomic analysis further reveals direct interactions between S100A4 and keratins critical for hair follicle and epidermal development (KRT5, KRT14, KRT8, KRT18), suggesting a structural and regulatory interface through which S100A4 modulates HFSC fate. Collectively, these results establish S100a4 as a central modulator of secondary HFSC function and provide mechanistic insight into the molecular control of hair follicle regeneration, with potential implications for improving cashmere fiber production. Full article
(This article belongs to the Special Issue Molecular Insights into Zoology)
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31 pages, 1515 KB  
Review
Regenerative Strategies for Androgenetic Alopecia: Evidence, Mechanisms, and Translational Pathways
by Rimma Laufer Britva and Amos Gilhar
Cosmetics 2026, 13(1), 19; https://doi.org/10.3390/cosmetics13010019 - 14 Jan 2026
Viewed by 7743
Abstract
Hair loss disorders, particularly androgenetic alopecia (AGA), are common conditions that carry significant psychosocial impact. Current standard therapies, including minoxidil, finasteride, and hair transplantation, primarily slow progression or re-distribute existing follicles and do not regenerate lost follicular structures. In recent years, regenerative medicine [...] Read more.
Hair loss disorders, particularly androgenetic alopecia (AGA), are common conditions that carry significant psychosocial impact. Current standard therapies, including minoxidil, finasteride, and hair transplantation, primarily slow progression or re-distribute existing follicles and do not regenerate lost follicular structures. In recent years, regenerative medicine has been associated with a gradual shift toward approaches that aim to restore follicular function and architecture. Stem cell-derived conditioned media and exosomes have shown the ability to activate Wnt/β-catenin signaling, enhance angiogenesis, modulate inflammation, and promote dermal papilla cell survival, resulting in improved hair density and shaft thickness with favorable safety profiles. Autologous cell-based therapies, including adipose-derived stem cells and dermal sheath cup cells, have demonstrated the potential to rescue miniaturized follicles, although durability and standardization remain challenges. Adjunctive interventions such as microneedling and platelet-rich plasma (PRP) further augment follicular regeneration by inducing controlled micro-injury and releasing growth and neurotrophic factors. In parallel, machine learning-based diagnostic tools and deep hair phenotyping offer improved severity scoring, treatment monitoring, and personalized therapeutic planning, while robotic Follicular Unit Excision (FUE) platforms enhance surgical precision and graft preservation. Advances in tissue engineering and 3D follicle organoid culture suggest progress toward producing transplantable follicle units, though large-scale clinical translation is still in early development. Collectively, these emerging biological and technological strategies indicate movement beyond symptomatic management toward more targeted, multimodal approaches. Future progress will depend on standardized protocols, regulatory clarity, and long-term clinical trials to define which regenerative approaches can reliably achieve sustainable follicle renewal in routine cosmetic dermatology practice. Full article
(This article belongs to the Section Cosmetic Dermatology)
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16 pages, 4362 KB  
Article
15-Hydroxyprostaglandin Dehydrogenase Inhibitor Restores Endothelial Function Under Dihydrotestosterone-Induced Stress in Human Dermal Microvascular Endothelial Cells
by Mujun Kim, Hak Joong Kim, Yurim Lee, Sanghwa Lee, Dong Chul Lim, Hee Dong Park and Dong Wook Shin
Molecules 2026, 31(1), 123; https://doi.org/10.3390/molecules31010123 - 29 Dec 2025
Cited by 1 | Viewed by 1744
Abstract
Androgenetic alopecia (AGA) is closely associated with oxidative stress and vascular dysfunction, which disrupt nutrient delivery to hair follicles and promote follicle miniaturization. Dihydrotestosterone (DHT) exposure impairs human dermal microvascular endothelial cell (HDMEC) function by inducing mitochondrial disruption, excessive reactive oxygen species (ROS) [...] Read more.
Androgenetic alopecia (AGA) is closely associated with oxidative stress and vascular dysfunction, which disrupt nutrient delivery to hair follicles and promote follicle miniaturization. Dihydrotestosterone (DHT) exposure impairs human dermal microvascular endothelial cell (HDMEC) function by inducing mitochondrial disruption, excessive reactive oxygen species (ROS) accumulation, and reduced angiogenic capacity. This study evaluated the protective effects of dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), a novel 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor identified through the AI-based discovery platform DeepZema®, in DHT-exposed HDMECs. DPP markedly reduced intracellular and mitochondrial ROS levels, restored mitochondrial membrane potential, and increased ATP production, thereby alleviating oxidative stress and supporting mitochondrial function. DPP also enhanced endothelial cell migration and capillary-like tube formation, demonstrating the restoration of angiogenic capacity that is essential for sustaining perifollicular vascularization. Moreover, DPP mitigated stress-associated signaling by reducing the phosphorylation of ERK, JNK, and p38 within the MAPK pathway, thereby suggesting the reestablishment of endothelial homeostasis under DHT-induced stress. Collectively, these findings indicate that DPP preserves endothelial function under DHT-driven oxidative conditions. We suggest that DPP may exert complementary protective effects on both vascular and follicular compartments, supporting its potential relevance in hair follicle regeneration. Full article
(This article belongs to the Special Issue Functional Molecules as Novel Cosmetic Ingredients)
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26 pages, 460 KB  
Review
Exosome-Based Therapies for Alopecia Areata: A Systematic Review of Clinical and Experimental Evidence
by Andra Irina Bulgaru-Iliescu, Dan Cristian Moraru, Alexandru-Hristo Amarandei, Stefana Avadanei-Luca, Mihai-Codrin Constantinescu, Alexandra Cristina Rusu and Mihaela Pertea
Int. J. Mol. Sci. 2026, 27(1), 21; https://doi.org/10.3390/ijms27010021 - 19 Dec 2025
Cited by 2 | Viewed by 3325
Abstract
Alopecia areata (AA) is an autoimmune-mediated nonscarring alopecia with limited therapeutic options and frequent relapses. Exosomes, nanosized extracellular vesicles secreted by various cell types, have recently emerged as potential regenerative and immunomodulatory therapies. The aim of the study is to review the clinical [...] Read more.
Alopecia areata (AA) is an autoimmune-mediated nonscarring alopecia with limited therapeutic options and frequent relapses. Exosomes, nanosized extracellular vesicles secreted by various cell types, have recently emerged as potential regenerative and immunomodulatory therapies. The aim of the study is to review the clinical and preclinical evidence regarding the efficacy and safety of EV-based therapies for alopecia areata. a systematic search of PubMed, Embase, Web of Science, and Cochrane Library was performed from 2020 to 2 October 2025. Inclusion criteria were original studies (clinical, preclinical, in vivo, in vitro) investigating exosome-derived interventions for AA. Outcomes of interest were hair regrowth, immune modulation, follicular regeneration, and safety. A total of 499 records were retrieved from electronic database searches. After deduplication and application of the inclusion/exclusion criteria, 40 studies met the eligibility criteria for the review. Of these, two were clinical studies (one retrospective cohort, one case report), while the remainder comprised five animal (in vivo) studies, six in vitro studies, and sixteen mixed translational studies (in vitro/in vivo ± clinical). Experimental studies reported hair coverage improvements of 50–99% and, in one instance, 30% regrowth in totalis and 16% in partialis, with nearly complete regrowth in incipient alopecia. Clinical reports noted density increases of 9–31 hairs per cm2 (e.g., from 121.7 to 146.6 hairs/cm2, p < 0.001) and improvements in hair count, length, and thickness. Several studies detailed activation of the Wnt/β-catenin pathway along with enhanced dermal papilla and hair follicle stem cell function, as well as anti-inflammatory effects. Reported safety profiles were favorable; when adverse events occurred, they were limited to mild, transient local reactions with no severe systemic issues. EV-based therapy is a novel and biologically plausible approach for AA, but robust randomized controlled trials (RCTs) are lacking. Standardization of small EV sources, doses, and delivery methods is essential before clinical translation. Full article
(This article belongs to the Section Molecular Biology)
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24 pages, 866 KB  
Review
Advancements in Bioactive Compounds and Therapeutic Agents for Alopecia: Trends and Future Perspectives
by Eunmiri Roh
Cosmetics 2025, 12(6), 287; https://doi.org/10.3390/cosmetics12060287 - 16 Dec 2025
Cited by 1 | Viewed by 4025
Abstract
Alopecia is a multifactorial disorder in which immune, endocrine, metabolic, and microbial systems converge within the follicular microenvironment. In alopecia areata (AA), loss of immune privilege, together with interferon-γ- and interleukin-15-driven activation of the JAK/STAT cascade, promotes cytotoxic infiltration, whereas selective inhibitors, including [...] Read more.
Alopecia is a multifactorial disorder in which immune, endocrine, metabolic, and microbial systems converge within the follicular microenvironment. In alopecia areata (AA), loss of immune privilege, together with interferon-γ- and interleukin-15-driven activation of the JAK/STAT cascade, promotes cytotoxic infiltration, whereas selective inhibitors, including baricitinib, ritlecitinib, and durvalumab, restore immune balance and permit anagen reentry. In androgenetic alopecia (AGA), excess dihydrotestosterone and androgen receptor signaling increase DKK1 and prostaglandin D2, suppress Wnt and β-catenin activity, and drive follicular miniaturization. Combination approaches utilizing low-dose oral minoxidil, platelet-rich plasma, exosome formulations, and low-level light therapy enhance vascularization, improve mitochondrial function, and reactivate metabolism, collectively supporting sustained regrowth. Elucidation of intracellular axes such as JAK/STAT, Wnt/BMP, AMPK/mTOR, and mitochondrial redox regulation provides a mechanistic basis for rational, multimodal intervention. Advances in stem cell organoids, biomaterial scaffolds, and exosome-based therapeutics extend treatment from suppression toward structural follicle reconstruction. Recognition of microbiome and mitochondria crosstalk underscores the need to maintain microbial homeostasis and redox stability for durable regeneration. This review synthesizes molecular and preclinical advances in AA and AGA, outlining intersecting signaling networks and regenerative interfaces that define a framework for precision and sustained follicular regeneration. Full article
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2025)
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59 pages, 3495 KB  
Review
Cannabidiol in Skin Health: A Comprehensive Review of Topical Applications in Dermatology and Cosmetic Science
by Aura Rusu, Andreea-Maria Farcaș, Octavia-Laura Oancea and Corneliu Tanase
Biomolecules 2025, 15(9), 1219; https://doi.org/10.3390/biom15091219 - 23 Aug 2025
Cited by 8 | Viewed by 13388
Abstract
Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L., has emerged as a promising multifunctional agent in dermatology and cosmetic science. The review provides an updated synthesis of CBD’s topical therapeutic potential, challenges, and evolving regulatory frameworks. CBD exhibits diverse biological effects, [...] Read more.
Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L., has emerged as a promising multifunctional agent in dermatology and cosmetic science. The review provides an updated synthesis of CBD’s topical therapeutic potential, challenges, and evolving regulatory frameworks. CBD exhibits diverse biological effects, including anti-inflammatory, antioxidant, antibacterial, analgesic, lipostatic, antiproliferative, moisturising, and anti-ageing properties through interactions with the skin’s endocannabinoid system (ECS), modulating CB1, CB2, TRPV channels, and PPARs. Preclinical and clinical evidence support its efficacy in managing acne, psoriasis (including scalp psoriasis), atopic and seborrheic dermatitis, and allergic contact dermatitis. CBD also relieves pruritus through neuroimmune modulation and promotes wound healing in conditions such as pyoderma gangrenosum and epidermolysis bullosa. In hair disorders such as androgenetic alopecia, it aids follicular regeneration. CBD shows promise in managing skin cancers (melanoma, squamous cell carcinoma, Kaposi sarcoma) and pigmentation disorders such as melasma and vitiligo. It enhances skin rejuvenation by reducing oxidative stress and boosting collagen and hydration. However, there are challenges regarding CBD’s physicochemical stability, skin penetration, and regulatory standardisation. As consumer demand for natural, multifunctional skincare grows, further research is essential to validate its long-term safety, efficacy, and optimal formulation strategies. Full article
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26 pages, 2100 KB  
Review
Recent Advances in the Role of Fibroblast Growth Factors in Hair Follicle Growth
by Junchao Wang, Lusheng Wang, Shuang Gao and Xiaokun Li
Biomolecules 2025, 15(8), 1198; https://doi.org/10.3390/biom15081198 - 20 Aug 2025
Cited by 4 | Viewed by 9562
Abstract
Hair follicles are essential to hair formation and cyclic regeneration, experiencing growth and degeneration, and quiescence phases involving complex signaling pathways. Among these, fibroblast growth factors (FGFs) play a critical role in follicular morphogenesis, but the role of FGF receptor signaling in hair [...] Read more.
Hair follicles are essential to hair formation and cyclic regeneration, experiencing growth and degeneration, and quiescence phases involving complex signaling pathways. Among these, fibroblast growth factors (FGFs) play a critical role in follicular morphogenesis, but the role of FGF receptor signaling in hair follicle development remains underexplored. Current treatments for hair loss, such as medical, surgical, light-based, and nutraceutical interventions, are often expensive, require long-term commitment, and are associated with substantial side effects. This review discusses the mechanisms and biological functions of the FGF signaling pathway within the hair follicle growth cycle, providing an overview of how these elements influence hair follicle dynamics and the pathogenesis of alopecia. Manipulating the FGF signaling pathway could offer new therapeutic options for androgenetic alopecia and other hair loss conditions, potentially exceeding current treatment modalities in efficacy and safety. Full article
(This article belongs to the Section Cellular Biochemistry)
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33 pages, 8604 KB  
Article
Sulforaphane-Rich Broccoli Sprout Extract Promotes Hair Regrowth in an Androgenetic Alopecia Mouse Model via Enhanced Dihydrotestosterone Metabolism
by Laxman Subedi, Duc Dat Le, Eunbin Kim, Susmita Phuyal, Arjun Dhwoj Bamjan, Vinhquang Truong, Nam Ah Kim, Jung-Hyun Shim, Jong Bae Seo, Suk-Jung Oh, Mina Lee and Jin Woo Park
Int. J. Mol. Sci. 2025, 26(15), 7467; https://doi.org/10.3390/ijms26157467 - 1 Aug 2025
Cited by 3 | Viewed by 6988
Abstract
Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on [...] Read more.
Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article
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18 pages, 5892 KB  
Article
CXCL12 Drives Reversible Fibroimmune Remodeling in Androgenetic Alopecia Revealed by Single-Cell RNA Sequencing
by Seungchan An, Mei Zheng, In Guk Park, Leegu Song, Jino Kim, Minsoo Noh and Jong-Hyuk Sung
Int. J. Mol. Sci. 2025, 26(14), 6568; https://doi.org/10.3390/ijms26146568 - 8 Jul 2025
Cited by 5 | Viewed by 3274
Abstract
Androgenetic alopecia (AGA) is a common form of hair loss characterized by androgen-driven tissue remodeling, including progressive follicular miniaturization and dermal fibrosis, which is accompanied by low-grade immune activation. However, the molecular mechanisms underlying this fibroimmune dysfunction remain poorly understood. Dermal fibroblasts (DFs) [...] Read more.
Androgenetic alopecia (AGA) is a common form of hair loss characterized by androgen-driven tissue remodeling, including progressive follicular miniaturization and dermal fibrosis, which is accompanied by low-grade immune activation. However, the molecular mechanisms underlying this fibroimmune dysfunction remain poorly understood. Dermal fibroblasts (DFs) have been suggested as androgen-responsive stromal cells and a potential source of CXCL12, a chemokine implicated in fibroimmune pathology, but their precise role in AGA has not been fully established. In this study, we performed single-cell transcriptomic profiling of a testosterone-induced mouse model of AGA, with or without treatment of CXCL12-neutralizing antibody, to elucidate the pathological role of CXCL12 in mediating stromal-immune interactions. Our analysis suggested that DFs are the primary androgen-responsive population driving CXCL12 expression. Autocrine CXCL12-ACKR3 signaling in DFs activated TGF-β pathways and promoted fibrotic extracellular matrix deposition. In parallel, paracrine CXCL12-CXCR4 signaling reprogrammed Sox2+Twist1+ dermal papilla cells (DPCs) and promoted the accumulation of pro-fibrotic Trem2+ macrophages, contributing to impaired hair follicle regeneration. Notably, CXCL12 blockade attenuated these stromal and immune alterations, restored the regenerative capacity of DPCs, reduced pro-fibrotic macrophage infiltration, and promoted hair regrowth. Together, these findings identify CXCL12 as a central mediator of androgen-induced fibroimmune remodeling and highlight its potential as a therapeutic target in AGA. Full article
(This article belongs to the Section Molecular Biology)
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19 pages, 6098 KB  
Article
Exogenous Alpha-Ketoglutaric Acid Alleviates the Rabbit Dermal Papilla Cell Oxidative Damage Caused by Hydrogen Peroxide Through the ERK/Nrf2 Signaling Pathway
by Xiaosong Wang, Shu Li, Jiali Chen, Lei Liu and Fuchang Li
Antioxidants 2025, 14(4), 455; https://doi.org/10.3390/antiox14040455 - 11 Apr 2025
Cited by 6 | Viewed by 2786
Abstract
As an endogenous metabolite, α-ketoglutarate (AKG) exhibits potent antioxidant properties, yet its molecular mechanisms remain unclear. Dermal Papilla Cells (DPCs), functioning as the regulatory hub of hair follicle morphogenesis, serve as a pivotal model system for deciphering follicular functionality and regeneration mechanisms through [...] Read more.
As an endogenous metabolite, α-ketoglutarate (AKG) exhibits potent antioxidant properties, yet its molecular mechanisms remain unclear. Dermal Papilla Cells (DPCs), functioning as the regulatory hub of hair follicle morphogenesis, serve as a pivotal model system for deciphering follicular functionality and regeneration mechanisms through their orchestration of signaling networks. Using a hydrogen peroxide (H2O2)-induced oxidative stress model in DPCs, we investigated AKG’s protective effects. AKG attenuated H2O2-triggered reactive oxygen species (ROS) overproduction, restored mitochondrial membrane potential, and suppressed apoptosis-related protein dysregulation. It enhanced cellular stress resistance by increasing the Bcl-2/Bax ratio, boosting antioxidant levels, and inhibiting inflammation. Mechanistically, H2O2 activated the Nrf2 pathway, while AKG amplified Nrf2 nuclear translocation and expression. Crucially, ERK inhibition abrogated AKG-mediated Nrf2 regulation, intensifying ROS accumulation and cell death. These results identify the ERK/Nrf2 axis as central to AKG’s antioxidative cytoprotection. This study advances AKG’s therapeutic potential and deepens insights into its multifunctional roles. Full article
(This article belongs to the Special Issue Antioxidant Effects of Natural Compounds on Cell Metabolism)
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18 pages, 918 KB  
Article
Therapeutic Potential of Gynostemma pentaphyllum Extract for Hair Health Enhancement: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
by Jihyun Lee, Yongxun Jin, Xinrui Zhang, Myoungrae Kim, Ayoung Koh, Shuyi Zhou, Changhyun Lee, Minji Seo, Shinjae Kim, Suye Jo, Youngjoo Kim, Seri Kwon, Kyuhan Kim and Chanyeong Heo
Nutrients 2025, 17(5), 767; https://doi.org/10.3390/nu17050767 - 21 Feb 2025
Cited by 6 | Viewed by 10117
Abstract
Background: Hair health critically influences both aesthetic appearance and psychological well-being. Existing treatments often show limited efficacy and may cause side effects. Gynostemma pentaphyllum (GP), known for its antioxidant and anti-inflammatory properties, has emerged as a promising botanical agent, although clinical evidence regarding [...] Read more.
Background: Hair health critically influences both aesthetic appearance and psychological well-being. Existing treatments often show limited efficacy and may cause side effects. Gynostemma pentaphyllum (GP), known for its antioxidant and anti-inflammatory properties, has emerged as a promising botanical agent, although clinical evidence regarding its hair health benefits remains limited. Purpose: This study aimed to evaluate the efficacy and safety of GP extract in improving hair parameters through a randomized controlled trial. Methods: This randomized, double-blind, placebo-controlled trial involved 100 eligible adults aged 19–60 years who were randomly allocated to either the GP or placebo group. Participants consumed 340 mL/day of the test product for 24 weeks. The primary outcomes included hair elasticity, density, diameter, glossiness, and subjective satisfaction. Safety was evaluated through laboratory tests and adverse event monitoring. Results: After 24 weeks, the GP group showed a threefold increase in hair elasticity and density and a fourfold increase in hair diameter compared to the placebo group. The subjective satisfaction scores corroborated these findings: the GP users reported better outcomes in terms of reducing hair damage and dryness. No significant differences in hair glossiness were observed based on the instrumental and visual assessments (p > 0.05). The safety evaluations revealed no severe adverse events. All the safety evaluation metrics demonstrated no significant abnormalities. Conclusions: This study provides compelling evidence of the efficacy of GP extract in enhancing hair health, demonstrating both significant functional improvements and an excellent safety profile. These findings substantiate its potential as a promising functional food ingredient for comprehensive hair care interventions. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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